The goal of this project is to evaluate the long-term efficacy of intraspinal microstimulation (ISMS) in restoring leg function after spinal cord injury (SCI). and to investigate certain aspects of neuronal and muscular plasticity induced by ISMS. The principal activity supported by this grant will be to provide spinal cord locations and stimulation parameters for long-term restoration of stable, weight-bearing standing and stepping after SCI. ISMS is expected to eliminate several of the difficulties associated with conventional peripheral nerve functional electrical stimulation (FES) systems used for augmenting limb movements in paralyzed individuals. The initial phase of the project entails mapping the lumbosacral region of the spinal cord during acute experiments in adult cats with complete spinal transections (T11) performed a week earlier. Once target locations within the spinal cord that yield reliable extensor and flexor limb movements after SCI are determined, 12 to 15 microwires will be chronically implanted in each side of the cord in intact cats. ISMS stimulus thresholds and elicited limb responses will be documented and the cats will be subsequently spinalized at T11. Patterned and tonic ISMS will be applied to generate weight-bearing standing and stepping of the hindlimbs. Stimulation sessions will take place 5 times per week (up to 6 months post-spinalization) and the quality of standing and stepping induced by ISMS will be assessed over time. Changes in the efficacy of reflex transmission will also be assessed throughout the experiments and will be used to estimate the level of ISMS-induce reorganization in spinal circuitry below the level of the lesion. The animals will then be euthanized and their spinal cords will be examined to determine the location of electrode tips and evaluate the effect of microwire implantation and long-term ISMS on neural damage. Immunohistochemical analysis of hindlimb muscles will be performed to determine the effect of ISMS on fiber type transformation. Finally, the efficacy of ISMS in generating functional limb movements under conditions of spastic hypertonus will be determined in adult rats with complete sacral cord transections rendering the tail paralyzed and spastic.